Circadian dysregulation induces alterations of visceral sensitivity and the gut microbiota in Light/Dark phase shift mice

作者：Lilin Hu, Gangping Li, Yan-Yun Shu, Xiaohua Hou, Ling Yang, Yu Jin · 发表于：Frontiers in Microbiology · 年份：2022 · DOI：10.3389/fmicb.2022.935919 · 被引用次数：42 · 研究领域：Gut microbiota and health、Circadian rhythm and melatonin、Barrier Structure and Function Studies

Background It is well-established that several features of modern lifestyles, such as shift work, jet lag, and using electronics at night, disturb normal circadian rhythm and increase the risk of suffering from functional gastrointestinal disease. Although substantial evidence demonstrates that shift work is closely correlated with the symptoms of visceral hypersensitivity, few basic studies have revealed the mechanism of visceral hypersensitivity induced by circadian rhythm disturbance, especially light/dark phase shifts. Our study explored the mechanism underlying visceral hypersensitivity caused by light/dark phase shift in mice. Methods A 6-h delay light/dark phase shift mice model was constructed. Visceral hypersensitivity was assessed by abdominal withdrawal reflex (AWR) score induced by colorectal distention (CRD) in vivo and contraction of colonic muscle strips induced by acetylcholine ex vivo . Intestinal permeability was evaluated by transepithelial resistance (TEER) and FD4 permeability. The expression of tight junction proteins was detected by western blotting and immunofluorescence staining. The gut microbiota was examined by 16S rDNA sequencing. Fecal microbiota transplantation (FMT) was performed to confirm the relationship between the light/dark phase shift, gut microbiota, and visceral hypersensitivity. Results We found that light/dark phase shift increased visceral sensitivity and disrupted intestinal barrier function, caused low-grade intestinal inflammatio...